Dose-Response Relationship of Oral Insulin Spray in Healthy Subjects
OBJECTIVE:--To evaluate the pharmacodynamic and pharmacokinetic properties and the dose-ranging effects of an oral insulin spray in comparison with subcutaneous regular insulin. RESEARCH DESIGN AND METHODS--In this randomized, five-way, cross-over study, seven healthy volunteers were assessed under...
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Published in | Diabetes care Vol. 28; no. 6; pp. 1353 - 1357 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.06.2005
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Subjects | |
Online Access | Get full text |
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Summary: | OBJECTIVE:--To evaluate the pharmacodynamic and pharmacokinetic properties and the dose-ranging effects of an oral insulin spray in comparison with subcutaneous regular insulin. RESEARCH DESIGN AND METHODS--In this randomized, five-way, cross-over study, seven healthy volunteers were assessed under euglycemic clamp and received four different doses of oral spray and one dose of subcutaneous regular insulin. RESULTS:--The time to maximum insulin concentration was shorter for oral insulin than for subcutaneous insulin (25.9 ± 9 vs. 145.7 ± 49.5 min, P < 0.05). Maximum serum insulin levels (C[subscript max]) were comparable between the subcutaneous and 20 puffs of oral insulin (39.1 ± 19.6 vs. 34.0 ± 7.4 [micro]U/ml, NS). The Ins-AUC₀₋₁₂₀ (area under the curve from 0 to 120 min for serum insulin) (339.8 ± 218, 681.3 ± 407, and 1,586.7 ± 8 [micro]U/ml, P < 0.05) and C[subscript max] (7.6 ± 2.8, 16.4 ± 9.3, and 39.1 ± 19.6 [micro]U/ml, P < 0.005) proved a dose-response relationship for the three doses of oral insulin (5, 10, and 20 puffs, respectively). Oral insulin had an earlier onset of action (31.7 ± 12 vs. 77.8 ± 3 min, P < 0.05), earlier peak (44.2 ± 10 vs. 159.2 ± 68 min, P < 0.05), and a shorter duration of action (85.1 ± 25 vs. 319.2 ± 45 min, P < 0.05) compared with subcutaneous insulin. The maximum metabolic effect (1.7 ± 1.0, 3.09 ± 1.7, and 4.6 ± 1.5 mg · kg⁻¹ · min⁻¹, P < 0.05) and the GIR-AUC₀₋₁₂₀ (amount of glucose infused from 0 to 120 min) (106.7 ± 74.3, 162.9 ± 116.1, and 254 ± 123 mg/kg) increased in a dose-dependent relationship for the three doses. CONCLUSIONS:--Oral insulin was absorbed in direct relation to the amount given and had a faster onset and a shorter duration of action compared with subcutaneous regular insulin. A dose-response relationship in the absorption and metabolic effect of the oral insulin was noted. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23 |
ISSN: | 0149-5992 1935-5548 |
DOI: | 10.2337/diacare.28.6.1353 |